Impaired T helper cell responses in human immunodeficiency virus‐exposed uninfected newborns

Abstract

Introduction: HIV-exposed uninfected (HEU) newborns suffer from higher risks of opportunistic infections during the first months of life compared to HIV-unexposed uninfected (HUU) newborns. Alterations in thymic mass, amounts of T helper (Th) cells, T-cell receptor diversity, and activation markers have been found in HEU newborns, suggesting alterations in T cell ontogeny and differentiation. However, little is known about the ability of these cells to produce specialized Th responses from CD4 + T cells. Method: To characterize the Th cell profile, we evaluated the frequency of Th 1

Premature skewing of T cell receptor clonality and delayed memory expansion in HIV-exposed infants

“…Both CD4 + and CD8 + T cell compartments in iHEU had lower frequencies of activated cells and memory differentiated cells expressing either PD-1 and/or perforin compared to iHUU. Although studies conducted before the wide adoption of perinatal ARV treatment reported heightened immune activation and/or exhaustion in iHEU 48 , 49 , more recent studies have shown reduced or impaired memory T cells among iHEU compared to iHUU 17 , 50 – 52 . Such T cell alterations were associated with poor responses to vaccines and/or increased hospitalisation 50 , 51 .…”

Immunologic consequences of maternal HIV infection in the uninfected newborn

“…We reported a decrease in the proportion of differentiated cells, both effector and suppressor cells. Interestingly, many of the T lymphocytes found are in undifferentiated stages (known as Th0), in which their activation by antigen-presenting cells did not complete 19 . This suggests that even though DCs are specifically characterized for maturing adaptive responses, despite being increased with higher levels of CD80 and CD86, they are not efficient in activating and maturing T cell responses.…”

Immune and Metabolic Alterations in Children with Perinatal HIV Exposure

“…The aberrant adaptive immune responses observed in CHEU may originate from alterations in T-cell ontogeny and differentiation [ 58 ]. Thymopoiesis, the process whereby T-cells mature and differentiate, takes place in the thymus.…”

“…The CHEU group had smaller subsets of Th 1 , Th 2 , Th 17 , and CD4+ CD25 + + (presumably Treg) T-cells compared to their unexposed counterparts. The reduced proportions of these Th cells found in CHEU resulted in impaired effector cytokine production [ 58 ].…”

“…Brito-Pérez et al observed that the number of Th 0 cells, defined as antigen-primed T-cells that do not gain an effector function despite stimulation from the TCR or locally associated cytokines, were elevated in CHEU. This would imply that the stimulation received by the T-cells is insufficient for them to differentiate into Th effector cells [ 58 ]. They postulate that this might be due to alterations in the in vivo effects that induce differentiation, mostly driven by the innate immune system.…”