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Delayed acquisition of Plasmodium falciparum antigen-specific CD4(+) T cell responses in HIV-exposed uninfected Malawian children receiving daily cotrimoxazole prophylaxis.

Longwe H, Phiri KS, Mbeye NM, Gondwe T, Mandala WL, Jambo KC - Malar. J. (2016)

Bottom Line: P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay.There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages.There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi. herbert.longwe@gmail.com.

ABSTRACT

Background: Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4(+) T cells-mediated immunity in HEU children is still not fully understood.

Methods: Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4(+) T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay.

Results: There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis.

Conclusion: The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells leads to higher risk to malaria disease remains unknown and warrants further investigation.

No MeSH data available.


Related in: MedlinePlus

Frequency of mycobacterium antigen specific CD4+ T cells in HEU and HUU children at different ages. a Total percentage of all IFN-γ cytokine producing CD4+ T cells was determined in HEU children and compared to HUU children at 6, 12 and 18 months of age. b Histogram comparing total percentage of all IFN-γ cytokine producing CD4+ T cells between HEU and HUU children overtime. c Total percentage of all TNF cytokine producing CD4+ T cells was determined in HEU children and compared to HUU children at 6, 12 and 18 months of age. d Histogram comparing total percentage of all TNF cytokine producing CD4+ T cells between HEU and HUU children overtime. X-axis represents time of visit. Black horizontal bars represent (a, c) mean with confidence intervals or (b, d) mean with SEM. Statistical significance was determined if p value was equal to or less than 0.05
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Fig5: Frequency of mycobacterium antigen specific CD4+ T cells in HEU and HUU children at different ages. a Total percentage of all IFN-γ cytokine producing CD4+ T cells was determined in HEU children and compared to HUU children at 6, 12 and 18 months of age. b Histogram comparing total percentage of all IFN-γ cytokine producing CD4+ T cells between HEU and HUU children overtime. c Total percentage of all TNF cytokine producing CD4+ T cells was determined in HEU children and compared to HUU children at 6, 12 and 18 months of age. d Histogram comparing total percentage of all TNF cytokine producing CD4+ T cells between HEU and HUU children overtime. X-axis represents time of visit. Black horizontal bars represent (a, c) mean with confidence intervals or (b, d) mean with SEM. Statistical significance was determined if p value was equal to or less than 0.05

Mentions: Next, it was hypothesized that if the lower frequency of P. falciparum antigen-specific CD4+T cells was due to generalized effects of CTX prophylaxis, then the frequency of mitogen-stimulated and antigen-specific CD4+ T cells in HEU children will also be lower than HUU age-matched controls. The results show that there was no difference in the frequency of mitogen-stimulated CD4+ T cells and the number of responders between HEU children and HUU age-matched controls at all ages (Fig. 4). It was also found that the frequency of mycobacterium-specific CD4+ T cells was not significantly different between HEU children and HUU age-matched controls at 12 and 18 months (Fig. 5). This suggests that the lower frequency of P. falciparum antigen-specific CD4+ T cells observed in HEU compared to HUU children was not generalized, but was specific to P. falciparum.Fig. 4


Delayed acquisition of Plasmodium falciparum antigen-specific CD4(+) T cell responses in HIV-exposed uninfected Malawian children receiving daily cotrimoxazole prophylaxis.

Longwe H, Phiri KS, Mbeye NM, Gondwe T, Mandala WL, Jambo KC - Malar. J. (2016)

Frequency of mycobacterium antigen specific CD4+ T cells in HEU and HUU children at different ages. a Total percentage of all IFN-γ cytokine producing CD4+ T cells was determined in HEU children and compared to HUU children at 6, 12 and 18 months of age. b Histogram comparing total percentage of all IFN-γ cytokine producing CD4+ T cells between HEU and HUU children overtime. c Total percentage of all TNF cytokine producing CD4+ T cells was determined in HEU children and compared to HUU children at 6, 12 and 18 months of age. d Histogram comparing total percentage of all TNF cytokine producing CD4+ T cells between HEU and HUU children overtime. X-axis represents time of visit. Black horizontal bars represent (a, c) mean with confidence intervals or (b, d) mean with SEM. Statistical significance was determined if p value was equal to or less than 0.05
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4862093&req=5

Fig5: Frequency of mycobacterium antigen specific CD4+ T cells in HEU and HUU children at different ages. a Total percentage of all IFN-γ cytokine producing CD4+ T cells was determined in HEU children and compared to HUU children at 6, 12 and 18 months of age. b Histogram comparing total percentage of all IFN-γ cytokine producing CD4+ T cells between HEU and HUU children overtime. c Total percentage of all TNF cytokine producing CD4+ T cells was determined in HEU children and compared to HUU children at 6, 12 and 18 months of age. d Histogram comparing total percentage of all TNF cytokine producing CD4+ T cells between HEU and HUU children overtime. X-axis represents time of visit. Black horizontal bars represent (a, c) mean with confidence intervals or (b, d) mean with SEM. Statistical significance was determined if p value was equal to or less than 0.05
Mentions: Next, it was hypothesized that if the lower frequency of P. falciparum antigen-specific CD4+T cells was due to generalized effects of CTX prophylaxis, then the frequency of mitogen-stimulated and antigen-specific CD4+ T cells in HEU children will also be lower than HUU age-matched controls. The results show that there was no difference in the frequency of mitogen-stimulated CD4+ T cells and the number of responders between HEU children and HUU age-matched controls at all ages (Fig. 4). It was also found that the frequency of mycobacterium-specific CD4+ T cells was not significantly different between HEU children and HUU age-matched controls at 12 and 18 months (Fig. 5). This suggests that the lower frequency of P. falciparum antigen-specific CD4+ T cells observed in HEU compared to HUU children was not generalized, but was specific to P. falciparum.Fig. 4

Bottom Line: P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay.There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages.There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Medical Sciences, College of Medicine, University of Malawi, Blantyre, Malawi. herbert.longwe@gmail.com.

ABSTRACT

Background: Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4(+) T cells-mediated immunity in HEU children is still not fully understood.

Methods: Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4(+) T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay.

Results: There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis.

Conclusion: The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells leads to higher risk to malaria disease remains unknown and warrants further investigation.

No MeSH data available.


Related in: MedlinePlus