Preservation of memory CD4(+) T lymphocytes in breast milk of lactating rhesus monkeys during acute simian immunodeficiency virus infection

Abstract

Acute human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) infection is associated with a massive depletion of memory CD4(+) T lymphocytes in the gastrointestinal tract. To define the dynamics of the CD4(+) T lymphocyte subpopulations in breast milk during acute HIV or SIV infection, lymphocyte populations were monitored in blood and milk of 4 Mamu-A*01(+) rhesus monkeys after SIVmac251 inoculation. Strikingly, although the CD4(+) T lymphocytes in blood were depleted during the peak of viremia, the milk CD4(+) T lymphocyte counts remained unchanged, despite active virus replication in the breast milk compartment. Moreover, CD4(+) memory T lymphocytes were preserved in breast milk during acute infection. CD4(+) T lymphocytes in breast milk and other mucosal compartments of uninfected monkeys were similar in their memory phenotype, activation status, and chemokine (C-C motif) receptor 5 expression. Interestingly, the number and proportion of effector CD8(+) T lymphocytes in milk were increased during acute SIV infection, suggesting effective control of virus-mediated CD4(+) T lymphocyte destruction in the breast milk compartment.

Figure 1

Absolute lymphocyte counts transiently decline in blood (A) and increase in milk (B) after SIVmac251 infection, but remain constant in milk of uninfected monkeys (C). Proportion of CD4+ T lymphocytes declines in blood (D) and milk (E) during acute SIVmac251 infection, but remains constant in milk of uninfected monkeys (F). The absolute number of CD4+ T lymphocytes is preserved in blood (G) and milk (H) after acute SIV infection and remains constant in milk of uninfected monkeys (I).

Figure 2

Breast milk CD4+ T lymphocyte counts remain constant despite robust SIV replication in the breast milk compartment. CD4+ T lymphocyte counts in breast milk (open circles) are displayed temporally with breast milk virus load (closed triangles) (A-D).

Figure 3

Memory CD4+ T lymphocyte subsets are unchanged in milk during acute SIVmac251 infection. The relative proportion of central memory (CD28+, CD95+), effector memory (CD28-, CD95+), and naïve (CD28+, CD95-) CD4+ T cells in blood (A, B, C) and milk (D, E, F) during acute SIVmac251 infection. The proportion of central memory (G) and effector memory (H) CD4+ T lymphocytes in blood (closed squares) and milk (open circles) at day 0 and 28 after SIVmac 251 infection.

Figure 4

CD4+ T lymphocytes in milk and other mucosal compartments in uninfected rhesus monkeys have a similar memory phenotype, CCR5-expression, and activation status. Proportion of total (A), central memory (B), effector memory (C), and naive (D) CD4+ T lymphocytes in mucosal compartments of uninfected monkeys. Proportion of total CD4+ T lymphocytes expressing the SIV coreceptor CCR5 in mucosal compartments of uninfected monkeys (E). Proportion of CD4+ T lymphocytes expressing CD25 (F) and MHC class II-DR (G) in mucosal compartments of uninfected monkeys.

Figure 5

Increase in virus-specific, CD8+ T lymphocytes in milk during acute SIVmac251 infection. The proportion of CD8+ T lymphocytes increases in blood (A) and milk (B) during acute SIVmac251 infection, but remains unchanged in milk of uninfected rhesus monkeys (C). Absolute numbers of CD8+ T lymphocytes in blood (D) and milk during acute SIVmac251 infection (E), and in milk of uninfected rhesus monkeys (F). Absolute numbers of Tat TL8-specific CD8+ T lymphocytes in blood (G) and milk (H) after acute SIV infection. Absolute numbers of Gag p11C-specific CD8+ T lymphocytes in blood (I) and milk (J) after acute SIV infection.

Figure 6

The proportion of SIV-specific, effector memory CD8+ T lymphocytes is increased in milk during acute SIVmac251 infection. Central memory (CD28+, CD95+), effector memory (CD28-, CD95+), and naive (CD28+, CD95-) proportions of CD8+ T lymphocytes in blood (A, B, C) and milk (D, E, F) during acute SIVmac251 infection. Central memory and effector memory Tat TL8-specific CD8+ T lymphocytes in blood (G, H) and milk (I, J) during acute SIVmac251 infection. Central memory and effector memory Gag p11C+ T lymphocytes in blood (K, L) and milk (M, N) during acute SIV infection.