CD8αα Expression Marks Terminally Differentiated Human CD8+ T Cells Expanded in Chronic Viral Infection.

The T cell co-receptor CD8αß enhances T cell sensitivity to antigen, however studies indicate CD8αα has the converse effect and acts as a co-repressor. Using a combination of Thymic Leukemia (TL) antigen tetramer, which directly binds CD8αα, anti-CD161, and anti-Vα7.2 antibodies we have been able for the first time to clearly define CD8αα expression on human CD8 T cells subsets. In healthy controls CD8αα is most highly expressed by CD161 "bright" (CD161++) mucosal associated invariant T (MAIT) cells, with CD8αα expression highly restricted to the TCR Vα7.2+ cells of this subset. We also identified CD8αα-expressing populations within the CD161 "mid" (CD161+) and "negative" (CD161-) non-MAIT CD8 T cell subsets and show TL-tetramer binding to correlate with expression of CD8ß at low levels in the context of maintained CD8α expression (CD8α+CD8ß(low)). In addition, we found CD161-CD8α+CD8ß(low) populations to be significantly expanded in the peripheral blood of HIV-1 and hepatitis B (mean of 47 and 40% of CD161- T cells respectively) infected individuals. Such CD8αα expressing T cells are an effector-memory population (CD45RA-, CCR7-, CD62L-) that express markers of activation and maturation (HLA-DR+, CD28-, CD27-, CD57+) and are functionally distinct, expressing greater levels of TNF-α and IFN-γ on stimulation and perforin at rest than their CD8α+CD8ß(high) counterparts. Antigen-specific T cells in HLA-B(∗)4201+HIV-1 infected patients are found within both the CD161-CD8α+CD8ß(high) and CD161-CD8α+CD8ß(low) populations. Overall we have clearly defined CD8αα expressing human T cell subsets using the TL-tetramer, and have demonstrated CD161-CD8α+CD8ß(low) populations, highly expanded in disease settings, to co-express CD8αß and CD8αα. Co-expression of CD8αα on CD8αß T cells may impact on their overall function in vivo and contribute to the distinctive phenotype of highly differentiated populations in HBV and HIV-1 infection.

Velopharyngeal function in nonsyndromic cleft palate: relevance of surgical technique, age at repair, and cleft type.

OBJECTIVE: The goal of this study was to determine the relative importance of surgical technique, age at repair, and cleft type for velopharyngeal function. DESIGN: This was a retrospective study of patients operated on by two surgeons using different techniques (von Langenbeck and Veau-Wardill-Kilner [VY]) at Children's Hospital, Boston, MA. PATIENTS: We included 228 patients who were at least 4 years of age at the time of review. Patients with identifiable syndromes, nonsyndromic Robin sequence, central nervous system disorders, communicatively significant hearing loss, and inadequate speech data were excluded. MAIN OUTCOME MEASURE: Need for a pharyngeal flap was the measure of outcome. RESULTS: Pharyngeal flap was necessary in 14% of von Langenbeck and 15% of VY repaired patients. There was a significant linear association (p = .025) between age at repair and velopharyngeal insufficiency (VPI). Patients with an attached vomer, soft cleft palate (SCP), and unilateral cleft lip/palate (UCLP) had a 10% flap rate, whereas those with an unattached vomer, hard/soft cleft palate (HSCP), and bilateral cleft lip/palate (BCLP) had a 23% flap rate (p = .03). Age at repair was critical for the unattached-vomer group (p = .03) but was not statistically significant for the attached-vomer group (p = .52). CONCLUSIONS: Surgical technique was not a significant variable either in aggregate or for the Veau types. Patients in the earliest repair group (8-10 months) were the least likely to require a pharyngeal flap. Early repair was more critical for HSCP and BCLP patients. There was no correlation between velopharyngeal insufficiency and Veau hierarchy. The attached vomer/levator muscle complex may be a more important predictor of surgical success than the anatomic extent of cleft.

Robin sequence: obstructive sleep apnea following pharyngeal flap.

OBJECTIVE: We reviewed 24 children with Robin sequence who underwent cleft palate repair. METHOD: All patients were 5 years of age or older at the time of review, allowing for accurate assessment of speech in relation to velopharyngeal function. All infants had palatal closure between 9 and 14 months of age, either V-Y repair (n = 16) or von Langenbeck repair (n = 8). RESULTS: Only 1 of 16 children who had V-Y repair had borderline velopharyngeal dysfunction (VPD). For reasons that are unclear, in the von Langenbeck repair group, six of eight children had VPD, and four of six underwent pharyngeal flap. Three additional patients with nonsyndromic Robin sequence had palatoplasty and subsequent pharyngeal flap. Six of the combined total of seven children with nonsyndromic Robin sequence developed obstructive sleep apnea and require flap take-down. CONCLUSION: Since conventional pharyngeal flap for VPD in nonsyndromic Robin sequence children resulted in a high incidence of obstructive sleep apnea, alternative management should be considered: modification of the standard pharyngeal flap, palatal lengthening (V-Y or double-opposing Z-plasty), or construction of a speech bulb.