Ratios of effector to central memory antigen‐specific CD4⁺ T cells vary with antigen exposure in HIV+ patients

Abstract

The OX40/CD25 assay is a novel technique that assesses antigen-specific CD4(+) T-cell responses. To unequivocally demonstrate that responding cells are memory cells that become activated after secondary stimulation, naïve CD45RA(+) and memory CD45RO(+) populations were stimulated with cytomegalovirus (CMV) lysate and the combined expression of CD25 and OX40 measured. As expected, the naïve population showed very little response, whereas there was a higher response from the memory counterpart. To further elucidate CD4(+) memory T-cell subsets involved in recall responses, CD4(+) T cells were separated into central memory (Tcm) and effector memory (Tem) subsets and stimulated with antigen-pulsed antigen-presenting cells (APCs). CMV responses in healthy donors showed a Tem-dominant response with a Tem/Tcm ratio of 1.2, whereas the tetanus toxoid responses were dominated by a Tcm response with a Tem/Tcm ratio of 0.35. To determine memory response in the chronic of HIV infection, patient samples were used. A similar pattern to healthy donors was observed in seven chronic HIV+ patients at week 4 after anti-retroviral therapy who responded to CMV with a larger response coming from Tem. The pattern was similar after 48 weeks of therapy but the responses were lower in magnitude. In chronic HIV+ patients who respond to Gag peptides, following institution of therapy there was an inversion of the ratio of the responding memory subsets compared with week 4, with a greater response from Tcm at week 48. This result was concordant with reduction in antigen load. As immune activation decreased there was also a decrease in the percentage of responding effector memory cells and maintenance of long-term central memory.

Human antigen‐specific CD4+CD25+CD134+CD39+ T cells are enriched for regulatory T cells and comprise a substantial proportion of recall responses

“…This is consistent with our previous finding that Ag-specific CD134 + CD25 + cells arise exclusively from the CD4 + CD45RO + memory T-cell population [33]. Across a range of Ag recall responses, these [34].…”

Individuals with inherited chromosomally integrated human herpes virus 6 (ciHHV-6) have functionally active HHV-6 specific T-cell immunity

“…For CMV, it has been shown that a higher viral inoculum as well as repeated viral replication re-stimulating the immune system leads to higher frequencies of specific T cells and to a late-stage driven T-cell response [14][15][16]. The T-cell response Upper part: Number (percentages) of individuals with U54-specific T-cell responses.…”

Hepatitis C‐specific effector and regulatory CD4 T‐cell responses are associated with the outcomes of primary infection

“…This three‐pool format has previously been validated against a 10‐pool format with the same peptides . Peptides were provided by BEI Resources (Manassas, VA, USA) and used at a final concentration of 1 μg/mL as previously described . Only genotype 1 peptides were used in this study as we previously reported that the great majority of subjects (96%) with CD4 responses to genotype 3 peptides also responded to genotype 1 peptides with generally larger magnitude responses.…”

“…40 Peptides were provided by BEI Resources (Manassas, VA, USA) and used at a final concentration of 1 μg/mL as previously described. 34,[41][42][43] Only genotype 1 peptides were used in this study as we previously reported 42…”